The control of food and water intake and the regulation of energy and water stores continue as the major focus of this project. Brain lesions profoundly affect food intake. We are exploring the concommitent effects of these lesions on gastric ulceration, fat mobilization and pancreatic hormone levels. In one study gastric ulceration following brain lesions could be prevented by anticholinergics and histamine antagonists. Localized brain transections which cause overeating and obesity do not cause hyperinsulinemia as do electrolytic lesions. These transections do impair the rats ability to mobilize fat. This suggests an important contribution of the sympathetic nervous system to weight regulation. The role of the parasympathetic nervous system has also been looked at by examining meal patterns through 24 hour cycles. Feeding is revealed to be controlled by different variables at different times of the day-night cycle. Insulin, if given steadily by an automatic, chronically implanted pump, can apparently increase the intensity of satiety cues and reduce overall food intake. This suggests that insulin may act normally as part of satiety mechanisms in hunger. A combination of electrophysiological and neuroanatomical techniques has identified a central pathway carrying information from hepatic osmoreceptors and sodium receptors. This pathway overlaps at several points a pathway handling taste information.